Hepatitis C Virus is a single stranded RNA virus that infects 170 million people world wide and the risk of contracting HCV is higher in Hispanics individuals. In fact, Hispanics are Associated with an aggressive course of Chronic Hepatitis C Infection. It causes chronic liver disease and cancer in approximately 80 % of infected individuals. Currently, there is no vaccine available and current therapies to treat this virus are costly, lengthy (6-12 months), associated with significant side effects, and result in sustained viral response by only 50% of the patients. The fundamental question in HCV research is how the virus establishes a persistent and productive infection in the host where there is no generalized immune deficiency. Answers to this question may lead to an understanding of how the virus persists in an immunocompetent host. A basic hypothesis is that HCV has developed strategies to evade the host's immune responses. The objective of this proposal is to elucidate the role of intracellular innate antiviral immunity in the co-evolution of HCV and host cells. If our central hypothesis is correct, we should be able to test novel approaches to shift the balance between HCV and hepatocytes in the setting of chronic infection toward an enhanced hepatocyte innate immune defense resulting in elimination of HCV from the human host.